Freeze drying of nested vials

Abstract

The present invention is directed to an improved lyophilization process wherein a plurality of vials is not in contact with the shelf of the lyophilization device. The present invention is further directed to lyophilization cake and intermediate cake obtainable according to the process of the invention.

1 . A method for lyophilizing a composition comprising lyophilizing a composition comprised in a vial, said vial being comprised in a plurality of vials housed by a device, said plurality of vials is preferably positioned adjacent to each other, preferably in a predetermined distance, wherein said vial comprising said composition to be lyophilized is not in direct contact with the shelf of a lyophilization device. 
     
     
         2 . The method of  claim 1 , wherein said device is separated from the shelf of said lyophilization device by a spacer, thereby said vial comprising said composition is not in direct contact with the shelf of a lyophilization device. 
     
     
         3 . The method of  claim 1 , wherein said vials are not in direct contact with the bottom of said device. 
     
     
         4 . The method of  claim 1 , wherein said vials are positioned or suspended in the device such that they are not in direct contact with the bottom of said device or with the shelf if the device has no bottom. 
     
     
         5 . The method of  claim 1 , wherein said vials have an inwardly curved bottom. 
     
     
         6 . The method of  claim 1 , wherein lyophilization, in particular primary and/or secondary drying, is carried out at shelf temperatures from about +10° C. to about +80° C. 
     
     
         7 . The method of  claim 1 , wherein lyophilization, in particular primary and/or secondary drying, is carried out at shelf temperatures from about +20° C. to about +60° C. 
     
     
         8 . The method of  claim 1 , where said method provides an essentially homogenous/defect-free lyophilized composition. 
     
     
         9 . The method of  claim 1 , comprising
 (a) providing at least one device formed to accommodate a plurality of vials positioned adjacent to each other in a predetermined distance, wherein at least one vial of said plurality of vials comprises a composition to be lyophilized;   (b) introducing said at least one device into a lyophilization device; and   (c) lyophilizing the composition to be lyophilized.   
     
     
         10 . The method of  claim 1 , wherein the device or vial comprises an insulating material. 
     
     
         11 . The method of  claim 1 , wherein said device is a nest array. 
     
     
         12 . A device formed to house a plurality of vials, preferably positioned adjacent to each other, preferably in a predetermined distance, wherein at least one vial of said plurality of vials is suitable to comprise a composition to be lyophilized, and
 (i) wherein said device is separated from the shelf of a lyophilization device by a spacer; or   (ii) wherein vials adjacent to said vial suitable to comprise a composition to be lyophilized are separated from the shelf of a lyophilization device by a spacer, or   (iii) wherein vials are separated from the shelf in that they are positioned or suspended in a device, e.g., by holders or racks such that their bottom is not in direct contact with the bottom of the device; or   (iv) wherein vials are separated from the shelf in that they are positioned in a device such that their bottom is not in direct contact with the shelf, if the device in which the vials are positioned may not have a bottom; or   (v) wherein vials adjacent to said vial suitable to comprise a composition to be lyophilized protrude beyond said vial suitable to comprise said composition.   
     
     
         13 . Use of a spacer in aiding in the preparation of an essentially defect-free lyophilized composition, wherein
 (i) said spacer is positioned between a device formed to accommodate a plurality of vials positioned adjacent to each other in a predetermined distance, wherein at least one vial of said plurality of vials is suitable to comprise a composition to be lyophilized, and a shelf of a lyophilization device, or   (ii) wherein said spacer is positioned between at least two vials adjacent to a vial suitable to comprise a composition to be lyophilized, and a shelf of a lyophilization device.   
     
     
         14 . A lyophilisate obtainable by the method of  claim 1  characterized in that said lyophilisate is essentially homogenous and free of structural defects in its bottom region. 
     
     
         15 . The method of  claim 3 , wherein said vials are positioned or suspended in the device such that they are not in direct contact with the bottom of said device or with the shelf if the device has no bottom. 
     
     
         16 . The method of  claim 2 , wherein the device or vial comprises an insulating material. 
     
     
         17 . The method of  claim 2 , wherein said device is a nest array. 
     
     
         18 . The method of  claim 4 , wherein the device or vial comprises an insulating material. 
     
     
         19 . The method of  claim 9 , wherein the device or vial comprises an insulating material. 
     
     
         20 . The method of  claim 9 , wherein said device is a nest array.